Flashcards in General Deck (500):
Inherited genetic defect leading to decreased chondrocyte proliferation in the growth plate of long bone
GOF mutation in FGF-R3 (cell signaling molecule) -> constant activation inhibits chondrocyte proliferation -> short limbs
What IL mediates anaphylactic rxn
IL-4 from Th2 cells
What does inulin VOD estimate
Extracellular fluid volume (so plasma + interstitial)
What does RISA VOD estimate
What does Cr-RBC estimate
What do D2O, antipyrine, or tritiated water estimate
Total body water
Sudden cardiac death from cocaine, what enzyme is elevated in myocardial cells prior to death?
PFK-1 - rate-limiting enzyme of glycolysis, b/c myocardial cells switch to anaerobic metab and glycolysis becomes the sole source of ATP
Formula to calculate steady state concentration
Dosing rate = Css x Clearance / F
F = 1 w/ IV
Starting with 285 mOsmol/kg H2O extracellular fluid osmolality and 42 L total body water, consume 3 L water and 10 mEq sodium, what's now the extracellular fluid osmolality?
Sodium consumed is very little so no effect (normal extracellular sodium conc is 140 mEq/L)
Consume 3 L so this will decrease (dilute out) extracellular osmolality by about 7% (3/42) --> so pick whatever is less than 285 mOsmol/kg but still in reasonable range
4-yo girl w/ ravenous apatite and rapid weight gain, floppy as a child, what's the finding on chromosome?
Abnormal methylation on chr 15
Difference bet what happens to APC and ras in colon cancer
Deletion or LOF mutation in APC (tumor suppressor)
ras is proto-oncogene so it would be amplified, induced, or have GOF mutation
What would you find in IgA deficiency on top of recurrent mucosal infection
Increased atopy (atopic allergy) -> switches to IgE more since can't make IgA
What would a pt w/ C3 deficiency be more susceptible to?
type III hypersensitivity - b/c it's immune complex mediated, and there's not enough C3 around to clear these complexes from blood stream
Ab against what structure in measles virus is protective?
The GC in LN contains cells undergoing what processs?
Where do you harvest saphenous vein?
Medial thigh inferolateral to pubic tubercle (branch off of external iliac vein)
Lateral foot sensation?
Medial foot sensation?
What kind of protein is n-MYC?
What kind of protein is k-RAS? And what pathway does it participate in?
GTPase (G-protein signaling)
Ras/MAP kinase pathway
How do you calculate attack rate?
Ratio of # of people who were exposed and developed illness over # of people who were exposed
Example: to calculate attack rate of potato salad, both top and bottom numbers will have to include people who had potato salad in combination with other things as well (not just potato salad alone)
Thymic aplasia + hypogammaglobulinemia in infancy. What's the defect?
Not common variable immunodeficiency because that wouldn't be so severe as to have thymic aplasia and that would present after neonatal period
What's responsible for variable presentations in 2 siblings w/ the same mitochondrial disease?
Heteroplasmy -> different organellar genomes (mutated and wild type) appearing w/in a single cell
What do most homeobox-containing genes code for?
Transcription factors that play a role in morphogenesis
Pt w/ ciliary dysfx, what's the disease association?
Kartagener's syndrome (half of pts w/ primary ciliary dyskinesia): persistent bronchial dilatation (bronchiectasis), situs inversus, male infertility, recurrent sinusitis/otitis
Defects in dynein arms (containing ATPase that generates energy for microtubules in cilia)
What enzyme in liver is important to be able to use TG breakdown product for energy and glucose synthesis?
Takes glycerol and converts it to glycerol 3-P, which is further converted to DHAP, which is fed into glycolysis (energy), gluconeogenesis, or used for TG synthesis in adipose tissue
Losing neutral aromatic AA in urine. Sx of ataxia, pruritic skin lesions and loose stools. What would sx most likely respond to?
Neutral aromatic AA is tryptophan, and the disease is Hartnup disease (intestinal and renal absorption of neutral AAs is defective) -> no tryptophan means no niacin synthesis -> niacin deficiency manifests as 3D's (dementia, diarrhea, dermatitis)
The naked RNA of what virus stays infectious on its own? Grows on nasal exudate
For a naked RNA to be infectious it needs to be SS+ (so equivalent to mRNA) -> able to use host's machinery for translation
If SS- or DS it needs a specific viral polymerase contained in complete virion
Formula for number needed to harm?
1 / attributable risk
Attributable risk = risk of developing disease if treated - risk of developing disease if untreated
Carrier frequency from mom's population is 1/30, carrier frequency from dad's population is 1/100. What's the probability of child having the disease if the disease is AR?
If mom is a carrier (Aa), the chance that she's passed on a recessive allele (a) is 1/2
So chance that mom is a carrier AND passed on recessive allele is 1/2 x 1/30
Similarly for dad = 1/2 x 1/100
So probability that both events will occur is a product of these 2 independent events = 1/2 x x 1/30 x 1/2 x 1/100 = 1/12000
What 4 things are Marfan pts susceptible of?
Mitral valve prolapse
Cystic medial degeneration of aorta (thus high risk for aortic root dilatation&aortic dissection -> most common cause of death after infancy)
Skeletal abnormalities (long extremities and fingers, scoliosis and/or kyphosis)
What do eosinophils contribute to host defense against schistosomiasis?
Ab-dependent cellular cytotoxicity (ADCC) -> because free IgE binds parasite first, then its heavy chain binds IgE Fc receptor on eosinophil surface -> eosinophils then release major basic proteins and enzymes from granules
This is NOT the same thing as type 1 hypersensitivity rxn, which eosinophils help regulate by degrading histamine (thus tones down severity) and facilitating inflammation. This type 1 rxn is mediated mainly by mast cells and basophils whose Fc receptor on the membrane is already bound to IgE (not free IgE) and are just waiting for Ag cross linking
What's a root cause analysis?
Identifies what, how, and why a preventable adverse outcome occurred -> collection of data thru interviewing ppl involved in the steps leading to the outcome
So if pt died bc he didn't receive the med he needs, the system based approach to fixing the problem is to interview pharmacy, nursing, med staff on the unit where this occurred (not jump right into creating alert system, etc)
What Ab differ most between IPV and OPV?
IPV is administered IM and is killed virus
OPV is administered orally and is live attenuated virus
OPV will generate more mucosal IgA (ie in intestine) because specific mucosal surface is directly stimulated by Ag (general principle that applies to all vaccine)
Little boy in fasting state developed seizure and was found to have hypoglycemia with low ketones
Acyl-CoA DH deficiency so can't make ketone bodies in fasting state
What are the 5 most important steps in preventing infection at central venous catheter?
Proper hand washing
Full barrier precautions during insertion
Chlorhexidine for skin disinfection (don't need to pretreat w/ antibiotic ointment or oral antibiotics)
Avoids femoral insertion site (subclavian best, internal jugular second best)
Removes catheter when no longer needed (but don't need scheduled catheter replacement)
Know exposure status (smoking), follow ppl for years and see if they develop cancer. What kind of study is this called?
Diff between retrospective cohort study and case control study
In retrospective cohort, exposure status is determined retrospectively and then they're tracked from that point (typically using medical records) -> exposure focused
In case control, you select pts w/ particular disease (cases), and without disease (control) (instead of selecting from exposure status) and look back to see if they were exposed -> disease focused
What should you remove from the diet of a child w/ aldolase B deficiency?
Sucrose (glu + fruc) and fructose
Given a graph of time vs. plasma concentration, and there are two lines, one for IV dose of drug (linear line w/ negative slope) and one for oral dose of drug (inverted asymmetric parabola). How do you calculate oral bioavailability?
Takes area under curve of oral graph and divide it by area under curve of IV graph
In reality, the calculation is F = (area under oral curve x IV dose) / (area under IV curve x oral dose)
Formula for relative risk calculation? What kind of study is it used for?
Risk among exposed divided by risk among unexposed
RR = a/(a+b) / c/(c+d)
For cohort study (study exposure) (relative rate can also be calculated for cohort study)
Formula for odds ratio calculation?
OR = a/c / b/d
For case-control study (study disease)
Homeless alcoholic man w/ cavitary lung lesion & air-fluid level. What most likely happened?
He aspirated oropharyngeal content.
NOT gastric content b/c that's more likely to cause chemical pneumonitis than lung abscess.
What enzyme fx primarily in the nucleolus?
Nucleolus is the site of ribosomal component synthesis and assembly (proteins made in cytosol transported in to assemble there)
RNA polymerase I is thus the enzyme (makes most of ribosomal components)
Where does parvovirus B19 replicate? What does it attach to?
Bone marrow (loves erythrocyte precursors) -> replication causes cell death
Attaches to erythroid cells via blood group P antigen (globoside)
What vitamin deficiency can manifest years after dietary insufficiency?
B12 (cobalamin) b/c huge liver reserve
Single nucleotide deletion results in decreased protein production. What mutation is this?
The other mutations (silent, missense, nonsense) are all caused by SUBSTITUTION not DELETION (or insertion)
Pt expressed DNR wish to spouse orally. Now incapacitated. How do you proceed?
ORAL DNR counts!
The correct answer is attend to pt's comfort and allow his family to be present w/ him as he is dying
When is it acceptable to treat or prescribe to family and friends?
not ALWAYS unethical to do so
Acceptable in emergency situations when no other physicians are available
What's a control in case-control study?
Ppl w/ no disease of interest REGARDLESS OF EXPOSURE
How do you get fast DNA replication in eukaryotes?
Multiple origins of replication (only single in prokaryotes)
What determines potency? What determines efficacy?
Potency: depends on affinity (higher affinity/lower ED50 -> more potent) and penetration -> left graph is more potent than right (shifting right w/ the same efficacy might be a result of the same basic pharmacologic agent but w/ a competitive antagonist mixed in)
Efficacy: Emax regardless of dose -> top graph is more efficacious than bottom graph
Stab wound perpendicular to skin above the clavicular between midclavicular and lateral sternal lines. What do you injure?
What's the one way you can get accessory nerve damage?
Surgery involving pos. triangle of neck (bound by clavicle, pos. border of sternocleidomastoid m., and ant. border of trapezius m.)
What's the one way you can get injury to ansa cervicalis? What are the nerve roots and what does it innervate?
Penetrating trauma to the neck above cricoid cartilage
Nerve roots C1-C3
Innervates the muscles in front of the neck: sternohyoid, sternothyroid, omohyoid m.
What's the one way you can get injury to carotid body?
Trauma to the level just inferior to the hyoid bone
Papillledema, dry skin, hepatosplenomeg. What's the vitamin abnormality?
Vitamin A excess
Older, mentally slow woman who is lemon colored, has a smooth tongue, and shuffling broad-based gait. What's the vitamin abnormality?
Vitamin B12 deficiency
Diarrhea, abd bloating, false negative stool guaiac. What's the vitamin abnormality?
Vitamin C excess
Hemorrhagic stroke in adults and necrotizing enterocolitis in children. What's the vitamin abnormality?
Vitamin E excess
Cheilosis, corneal vascularization, stomatitis, glossitis, dermatitis. What's the vitamin abnormality?
Vitamin B2 (riboflavin) deficiency
Pellagra sx? Vitamin defect?
3 D's: Diarrhea, Dermatitis, Dementia
Vit B3 (niacin) deficiency
Branches of thyrocervical trunk?
Inf thyroid artery
Superficial cervical artery
(it's a trunk off of subclavian artery)
What does recurrent laryngeal nerve loop around on the left and the right?
R = subclavian arter (between the subclavian vein and artery)
L = arch of aorta
What 5 cytokines recruit neutrophils?
IL-8 (secreted by macrophages), leukotriene B4 and 5-HETE, C5a, n-formylated peptides
What does C3a do?
Recruits eosinophils and basophils
Also stimulates mast cell histamine release
What does C5a recruit?
Capillary hemangioblastoma in the retina/cerebellum + pheochromocytoma + clear cell renal carcinoma + cysts of kidney, liver, and/or pancreas. What's the disease?
Could be tuberous sclerosis if it's cortical/subependymal HAMARTOMAS
Cortical/subependymal hamartomas + cysts of kidney, liver, and/or pancreas + cardiac rhabdomyosarcoma + adenoma sebaceum (cutaneous angiofibroma) + renal angiomyolipoma + ash-leaf skin patches. What's the disease?
Seizure is the major complication
Congenital telangiectasias (creating epistaxis, GI bleed, hematuria). What's the disease?
Osler-Weber-Rendu syndrome (AD hereditary hemorrhagic telangiectasia)
Cutaneous facial angiomas (facial port-wine stain) + leptomeningeal angioma (capillary venous malformation) + V1&V2 skin involvement + tram-track calcification of skull. What's the disease?
Sturge-Weber syndrome (encephalotrigeminal angiomatosis)
Exquisite ear pain and drainage + granulation tissue w/in ear canal + intact tympanic membrane. What's the causal org? What pt population?
Pseudomonas aeruginosa (motile, oxidase positive G- rod)
This condition is called malignant otitis externa (MOE) - contrast this to acute otitis media, which affects tympanic membrane and is caused by H influenzae
Pt population: elderly diabetics
Inflamed, bulging, erymathous, nonmotile tympanic membrane + infected fluid in middle ear. What's the causal org? What pt population?
This condition is called acute otitis media, contrast to malignant otitis externa, which doesn't affect tympanic membrane
Pt population: kids and adults
Athralgia + brown spots on sclerae + diffuse darkening of helix of ears. What's the disorder and enzyme defect?
Alkaptonuria (most characteristic thing is urine turns black when exposed to room air - bc homogentisic acid is oxidized)
In elevator with a bunch of people, hospitalist asked if you got a brain CT result on pt in room 200. What do you do?
"Let's step off the elevator and discuss it"
CANT acknowledge that the pt had a brain scan ("I have the results and can call you later" or "The scan was read, ask the resident on duty for the results") and DONT admonish colleague in the elevator
What AA is used to make serotonin?
What 5 molecules is tyrosine a precursor of?
What 4 molecules is methionine a precursor/intermediate of?
3 ways Aspergillus messes stuff up and pt population for each category
1) Invasive aspergillosis: hemoptysis, pleuritic chest pain & fever, necrotizing pneumonia, granuloma -> those w/ immunocompromised, neutropenia, and chronic granulomatous disease are susceptible
2) Allergic bronchopulmonary aspergillosis (ABPA): bronchiectasis, eosinophilia, migratory pulm infiltrates, increased IgE and Ab -> those w/ asthma and CF are susceptible
3) Aspergillomas: seen on CXR as radiopaque structure that shifts when pt changes position, colonizing existing lung cavities (such as after TB), can cause hemoptysis
What do you call T cells that are negative for both CD4 and CD8?
What do you call T cells that are positive for both CD4 and CD8?
Immature T lymphocyte
Where does positive selection of T cells occur and what cells does it need?
Positive selection: cells that binds to self MHC are allowed to SURVIVE
Needs thymic epithelial cells
Where does negative selection of T cells occur and what cells does it need?
Negative selection: cells that bind w/ high affinity to self Ag DIE
Needs thymic medullary epithelial cells and dendritic cells
Differences between macrophages and B cells in terms of Ag presentation
Macrophages: inducably express MHCII and B7; can only stimulate effector or memory T cells, not naive T cells
B cells: constitutively express MHCII, can stimulate all types of T cells
Heterophile Ab positive. What's the org?
5 diseases assc. w/ EBV?
Burkitt lymphoma (endemic, African type)
Nasopharyngeal lymphoma (Chinese)
CNS lymphoma (AIDs pts)
Post-transplant lymphoproliferative disorder
See increased MMP activity + fibroblasts in wound 3 weeks out. What's the related possible complication?
What is t-test used for?
Differences bet. MEANS of 2 groups
What is ANOVA (analysis of variance) used for?
Differences bet. MEANS of 3 or more groups
What is chi-square used for?
Difference bet. 2 or 3 percentages or proportions of CATEGORICAL outcomes (not mean values)
What is Pearson correlation coefficient? And what does this tell you exactly?
r value in linear correlation (always between -1 and +1)
Tells you how well the data fit to the linear regression -> NO RELATION to magnitude of slope
What is coefficient of determination?
r^2 (Pearson correlation coefficient squared) -> value that's usually reported
HIV pt came in w/ CMV retinitis. Treated and is now having generalized seizure, hypocalcemia, hypomagnesemia. What was the drug? And why was that drug used over other CMV drugs?
Foscarnet (Ca2+ chelation -> renal wasting of magnesium -> hypomagnesemia -> decreased PTH -> even lower Ca2+ -> seizure)
Prefer foscarnet over the usual ganciclovir in CMV retinitis assc. w/ HIV b/c HIV pts are usually on zidovudine which causes bone marrow suppression. Ganciclovir causes severe neutropenia that can worsen that.
Mom and daughter are incapacitated and need blood transfusion. Called father and he said they're Jehova's witnesses. Father hung up before physician can ask about giving blood product, and mom and daughter are not carrying a card that confirms religious belief. What do you do?
Give blood to both mom and daughter
Mom: would have had the rights to refuse life-saving treatment had she not been incapacitated, but she is and next of kin surrogate decision maker (husband) can't be reached. So can give blood to her
Daughter: always give life-saving therapy in emergency situations regardless of parents' wishes
Th1 (stimulation, secretion & fx, inhibition)
Stimulated by: IL-12 (from macrophages)
Secretion: IFN-g and IL-2 -> activates macrophages and CD8 T cells
Inhibited by: IL-4, IL-10 (from Th2)
Th2 (stimulation, secretion & fx, inhibition)
Stimulated by: IL-4, IL-10
Secretion: IL-4, IL-5, IL-6, IL-13 -> recriots eosinophils and promotes IgE production
Inhibited by: IFN-g (from Th1)
IL-1 (origin and 2 fx)
Secreted by: macrophages
Fx: osteoclast-activating factor, fever & acute inflammation (activates endothelium to express adhesion molec, recruits leukocytes by inducing chemokine secretion)
IL-6 (2 origins and fx)
Secreted by: macrophages, Th2
Fx: fever (stimulate production of acute-phase protein)
IL-8 (origin and fx)
Secreted by: macrophages
Fx: chemotactic factor for neutrophils
IL-12 (2 origins and 2 fx)
Secreted by: macrophages, B cells
Fx: differentiation of T cells into Th1, activates NK
TNF-a (origin, 2 fx, disease assc.)
Secreted by: macrophages
Fx: septic shock, activates endothelium (leukocyte recruitment and vascular leak), mediates paraneoplastic cachexia (by suppressing appetite in hypothalamus, inhibiting lipoprotein lipase, and increasing insulin resistance in peripheral tissues)
Disease assc: RA, psoriatic arthritis, TB
IL-2 (origin and fx)
Secreted by: EXCLUSIVELY lymphocytes -> secreted by all T cells (so deficiency in IL-2 RECEPTOR -> SCID) -> first thing T cells produce after coming in contact w/ Ag
Fx: growth&differentiaion of T cells, B cells, NK, and macrophages
IL-3 (origin and fx)
Secreted by: all T cells
Fx: growth & differentiation of bone marrow stem cells (fx like GM-CSF tha's produced by all kinds of cells -> macrophages, T cells, NK, mast cells, endothlial cells, fibroblasts)
IFN-g (origin and 3 fx)
Secreted by: Th1
Fx: activates macrophages, antiviral (activates NK), antitumor, increases MHC expression and Ag presentation in all cells
IL-4 (origin and 3 fx)
Secreted by: Th2
Fx: Th2 differentiation, B cell growth, class switching to IgE and IgG
IL-5 (origin and 3 fx)
Secreted by: Th2
Fx: B cell differentiation, class switching to IgA, growth & differentiation of neutrophils, growth&differentiation of neutrophils
IL-10 (2 origins and fx)
Secreted by: Th2, regulatory T cells
Fx: downregulates inflammatory responses, inhibits activated T cells and Th1 (similar actions to TGF-B b/c anti-inflammatory)
What's the most common cause of pseudotumor cerebri in teenagers?
Tetracycline (for acne)
What system do you see cGMP-gated Na+ channels?
B1 receptor effector & organ system
Gs -> increases cAMP
Heart, kidney (renin release)
B2 receptor effector & organ system
Gs -> increases cAMP
Lungs, insulin release, decreases uterine tone, relaxes CILIARY MUSCLE (thins lens to focus on distant vision), increases aq humor production
Vasodilation, lipolysis, heart (increases HR)
a1 receptor effector & organ system
Gq -> increases IP3
Vasocontriction, contracts PUPILARY MUSCLE (MYDRIASIS), contracts intestinal and bladder sphincter
a2 receptor effector & organ system
Gi -> decreases cAMP
Increases platelet aggregation
Decreases sympa outflow, insulin release, lipolysis
M1 receptor effector & organ system
Gq -> increases IP3
CNS & ENS
M2 receptor effector & organ system
Gi -> decreases cAMP
Heart (decreases HR and contraction)
M3 receptor effector & organ system
Gq -> increases IP3
All other things besides heart and CNS&ENS -> secretions (incl insulin!), gut motility, bladder, bronchoconstriction,
Contracts CILIARY MUSCLE (so effect opposite of B2) (makes lens round to focus on near vision -> accommodation)
D1 receptor effector & organ system
Gs -> increases cAMP
Renal vascular smooth muscle (relaxes)
D2 receptor effector & organ system
Gi -> decreases cAMP
Modulates transmitter release
H1 receptor effector & organ system
Gq -> increases IP3
Nasal&bronchial mucus, vascular permeability, pruritus, pain, bronchiole contraction
H2 receptor effector & organ system
Gs -> increases cAMP
V1 receptor effector & organ system
Gq -> increases IP3
Increases vascular smooth muscle contraction
V2 receptor effector & organ system
Gs -> increases cAMP
Increases H2O permeability in kidney
5 things that Down pts are more at risk for
Leukemia (AML - acute megakaryoblastic leukemia subtype before 5 yo, ALL after 5 yo)
Congenital heart defects (esp VSD & endocardial cushion defects -> ostium primum ASD, regurgitant AV valves from cleft in ant leaflet of mitral or septal leaflet of tricuspid)
Duodenal atresia (NOT other segments)
Early onset Alzheimer
Differences in immune response when using killed viral vaccine and live attenuated viral vaccine?
Killed viral vaccine: humoral immune response -> Ab generated to neutralize virus and prevent it from ENTERING cells (killed virus can't actually infect host cells)
Live-attenuated viral vaccine: virus actually enters cells and stimulates MHC I pathway -> CD8+ cells kill infected cells in future exposures
What age should ppl start being vaccinated w/ flu vaccine?
> 6 mo
What do interferon a and b do specifically?
Suppressing viral REPLICATION and ASSEMBLY
Cause of wrinkles?
Decreased collagen SYNTHESIS and elastin
Thinning of dermis & epidermis + flattening of dermoepidermal jx
Decreased # of fibroblasts
NOT decreased proline hydroxylation or collagen cross-linking, etc
Physician is paid fixed amount per enrollee. So there's incentives to providing preventive care.
Commonly used by HMOs (as opposed to fee-for-service or discounted fee-for-service, which is used in preferred provider organization type)
How is botulinum toxin released? How do you dx?
It's contained inside cell and released w/ autolysis (so NOT actively secreted)
Detecting toxin in stool (ELISA and PCR)
3 D's of botulinum toxin poisoning
In 12-46 hrs
Lacks multiple enzymes containing lipoic acid subunit. Most likely finding?
Need this as cofactor for pyruvate DH, alpha ketoglutarate DH, and alpha ketoacid DH
So most important finding would be lactic acidosis, because you don't have pyruvate DH to bridge glycolysis to TCA, so pyruvate gets shunted to make lactate instead
Yeast and pseudohyphae on LM + positive germ tube test?
Candida albican (germ tube test used to differentiate it from other Candidas)
What does cutaneous candidiasis look like?
Erythema, vesiculopapular rash, maceration, fissuring
Oval yeast cells w/in macrophages. Caseating granulomas in tissues. What fungus?
Bird or bat droppings. What fungus?
Broad-base budding + thick, doubly refractive walls?
The incidence of what fungal infection goes up after earthquake?
Spherule filled w/ endospores found in granulomas?
Budding yeast w/ captain's wheel formation + Latin America
Irregular, broad, nonseptate hyphae branching at wide angles?
Disc-shaped yeast on methenamine silver stain?
Pneumocystis jirovecii (PCP)
Dimorphic, cigar-shaped budding yeast living on vegetation?
Rose gardener's disease. What fungus?
Most common causes of hepatic abscesses in developed countries? Developing countries?
Developed countries -> consider bacterial
Hematogenous: S. aureus
Ascending cholangitis/portal vein pyemia/direct invasion from adjacent area: E. coli, Klebsiella, enterococci
Developing countries -> consider parasites
Entamoeba (ascending from the colon thru portal venous system), echinococcal
Acute transplant rejection timeline and histology?
Timeline: w/in 6 months
Histology: either cell-mediated or Ab-mediated -> so see lymphocyte infiltration
Conditions assc w/ low or high AFP during pregnancy
High AFP: omphalocele, multiple gestation, body wall defect (gastrochisis), neural tube defect
Low AFP: Down -> do amniotic karyotyping for definitive dx next
Percentage values for 1SD? 2SD? 3SD?
Infection w/ what group of orgs should be assc. w/ "impaired intracellular killing"
Catalase-positive stuff -> so staph
Impaired cellular killing -> chronic granulomatous disease -> recurrent cutaneous abscesses
Why is having too much IgA put you at risk for disseminated N. meningitidis infection?
IgA binds to bac and prevents them from attaching to mucosal surface, but doesn't activate complement killing like IgM and IgG do -> complement activation is a more effective form of killing b/c it's actually bacteriocidal
Start and stop codons?
Start: AUG -> methionine
Stop: UAA, UAG, UGA -> "releasing factor" recognizes these codons
Read mRNA from its 5' -> 3'
What does elongation factor do?
Facilitates tRNA binding and translocation steps of protein synthesis
What does transcription factor II D do?
Binds TATA promoter region upstream from the gene's coding region
Patient w/ signs of domestic violence who is in denial ("I'm sure it won't happen again"). What should you say?
"Do you have a safe place to go in an emergency?"
The focus should be to ask open-ended, nonjudgmental questions, and to assess immediate and future safety. DONT counsel patients in directive way or ask why she stays in a relationship
Describe histologic characteristics of koilocytes (besides resinoid appearance)
Immature squamous cell w/ enlarged pyknotic nucleus, irregularly staining cyto, and perinuclear vacuoles (PERINUCLEAR CLEARING)
Pap smears show predominance of parabasal cells. What does this mean and what do parabasal cells look like?
Means it's from post-menopausal and post-partum women
They're round cells w/ BASOPHILIC cyto, finely granular chromatin in nuclei, high N/C ratio
Normal glandular endocervical cells on Pap smear. What does this mean and what do normal glandular cells look like?
Indicates ADEQUATE sampling
They're columnar cells w/ vacuolated/granular cytoplasm, prominent cell border -> forming HONEYCOMB pattern when clustered together
2 other names for alpha toxin from C. perfringens? What does it do?
Lecithinase, phospholipase C
Loss of cell membrane integrity -> increases platelet aggregation and adherence molecule expression (on leukocytes and endothelium) -> vasoocclusion & ischemic necrosis of tissues
What 4 things does pertussis toxin (AB toxin) do?
Inhibits Gi (by ribosylating it) so increases cAMP -> get
Massive lymphocytosis (chemokines disabled) -> so lymphocytes can't come to tissues -> same as lymphocyte destruction??
Increased sensitivity to histamine
Mechanism behind rheumatic fever? (brief)
Autoimmune activation by antigen mimicry (GAS and myocytes have similar antigenic protein sequences)
Example of X-linked dominant disease?
Hypophosphatemic rickets -> phosphate wasting at proximal tubule
3 examples of mitochondrial inheritance pattern?
Myoclonic epilepsy w/ ragged red fibers (MERRF): from failure in oxidative phosphorylation (myopathy + lactic acidosis + CNS disease)
Leber hereditary optic neuropathy
Mitochondrial encephalopathy w/ stroke-like episodes and lactic acidosis (MELAS)
Pt's serum is mixed w/ solution of cardiolipin, lecithin, and cholesterol and flocculation is considered positive test. What test is this called and what would it be positive for?
RPR test (VDRL) for syphilis -> screening test so needs confirming by FTA-ABS
Pt's blood is added to tube pretreated w/ anticoagulant (EDTA) and tube is placed in a cup of ice. Agglutination is considered positive. What test is this called and what would it be positive for?
Cold agglutinins for Mycoplasma, EBV, hematologic malignancies
What's one way to deplete carnitine and impair beta-oxidation of FA?
Excessive alcohol consumption
S. aureus cultured from urine. What should you suspect?
S. aureus doesn't usually cause UTI, so suspect metastatic infection from other sites such as abscesses or infective endocarditis
What to say when pt wants antibiotics for viral illness?
Don't prescribe b/c of potential risks of drug (and antibiotic resistance problem)
What are the fx of 2 diphtheria toxins? Which one induces immune response?
Exotoxin B: binds specifically to heparin-binding EGFR on cardiac and neural cells (selectivity) and allow penetration of A subunit -> production of circulating IgG is against this subunit
A subunit: active subunit that ribosylates ADP of EF-2 and inhibits protein synthesis
3 disorders of myopathies w/ elevated creatine kinase? 2 disorders w/ normal creatine kinase?
Myopathies w/ elevated creatine kinase: inflammatory myopathies (polymyositis, dermamyositis), statin-induced myopathy, hypothyroid myopathy (myoedema characteristic)
Myopathies w/ normal creatine kinase: glucocorticoid-induced myopathy (weakness/atrophy w/out pain), polymyalgia rheumatica (pain&stiffness worse in morning & w/ activity)
4 virulence factors produced by P. aeruginosa
Exotoxin A: protein synthesis inhibition
Elastase: for vessel destruction
Phospholipase C: degrades cellular membranes
Pyocyanin: generates reactive oxygen species -> kill competing microbes
What is Klebsiella usually assc. w/ in elderly and immunocompromised?
When should advance directives be discussed and what are their 2 main components?
Ideally in outpatient setting w/ primary care, but ESPECIALLY when pt is hospitalized (get over the awkwardness)
Components: living will and health care proxy
3 basic AAs?
"His Arguments are based on Lies"
Histidine (no charge at body pH), Arginine, Lysine
How do you calculate charges on AA?
At pH above pKa, proton dissociates from AA -> so carboxyl group and ammonium groups exist as COO- and NH2
So pH below pKa, they exist as COOH, NH3+
What is MacConkey agar and what orgs does it restrict?
Bilt salt-containing agar
Restricts growth of most G+
Colony turns pink-red if ferments lactose
2 other names for Thayer-Martin VCN medium?
Heated blood agar
What is Bordet-Gengou medium used to grow?
What fungal infections are assc. w/ recent antibiotic use?
Superficial Candida (oral thrush or vulvovaginitis)
What fungal infections are assc. w/ animal contact?
Dermatophytoses caused by Microsporum species (tinea capitis)
Describe lesions caused by Sporothrix? Histology?
Reddish nodule that later ulcerates -> fungus spreads along lymphatics forming subQ nodules and ulcers
Granuloma consisting of histiocytes + giant cells + neutrophils, surrounded by plasma cells
What Ig bind complement and what specific region binds to it?
IgM and IgG -> IgM is better at it b/c it circulates in pentameric form (monomeric for IgG) -> good b/c C1 needs 2 Ig domains for activation
C1 binds to Fc region NEAR THE HINGE POINT (the farther carboxyl region is for Fc receptor on phagocytes, and for J chain that join multiple IgA or IgM together so they cancirculate in dimeric or pentameric form) -> so complement activation by IgM before Ag binding is prevented form happening by the fact that this region is hidden while unbound IgM is circulating in its planar form
3 cytogenetic abnormalities that can lead to Down
1. Trisomy 21 (meiotic nondisjunction IN OVUM)
2. Unbalanced Robertsonian translocation (extra arm of 21 is attached to another chromosome) -> so have normal # of chromosomes
3 genetic syndromes caused by deletions?
Cri du chat (5p)
What is impaired in hyper-IgM syndrome?
Immunoglobin gene rearrangement
Loss of follow up occurs disproportionately bet. the exposed and unexposed group. What bias might occur?
Attrition bias (type of selection bias)
Does NOT occur if loss of follow up happens proportionately to both groups
Sx of pyridoxine (B6) deficiency? What 2 drugs can induce this?
Peripheral neuropathy, convulsion, dermatitis, sideroblastic anemia (need this to synthesize Hb), iron excess
Drugs that induce: INH, OCPs
Bacterial ribosomal components and their fx?
30S ribosomal subunit: has 16S rRNA -> holds sequence complementary to Shine Dalgarno sequence (present in all prokaryotic cells and is upstream from AUG sequence) -> necessary for protein translation initiation
50S ribosomal subunit: has 23S rRNA -> peptidyltransferase activity
Elongation factor G: translocation of protein, energy supplied by GTP
A site: binds incoming aminoacyl-tRNA
Where is aminoacyl-tRNA synthetase in the cell?
Cytosol, each specific for particular AA/tRNA pair
Formula for calculating HL from VD and Cl? How many HL does it take to virtually eliminate a drug?
t1/2 = 0.7 x VD/CL
VD = vol of distribution
Cl = clearance
Takes about 5 HLs to virtually eliminate a drug/establish SS conc
What agar do you use to grow V cholerae?
TCBS agar -> very alkaline selective media
What does a vaccine for V cholerae stimulate and what kind of vaccine is it?
Killed bacteria (same as Yersinia pestis vaccine)
What vibrio orgs are ppl w/ chronic liver disease susceptible to?
V. vulnifics from wound infection, but can also get from oyster
Difference between effect modification and confounding bias?
Stratified analysis (analyze cohort as a diff subgroup) will show statistical significance in effect modification, but not in confounding bias
Effect modification is NOT a bias but a natural phenomenon
7 AAs w/ 3 titratable protons?
Histidine, arginine, lysine, glutamate, aspartate, cysteine, tyrosine
Features of Patau?
Characteristic midline stuff (Patau for "Parting"): cleft lip/palate, holoprosencephaly, coloboma, abdominal wall defects
Other stuff: POLYDACTYLY, polycystic kidney disease, rocker bottom feet (see this in Edwards too), umbilical hernia, pyloric stenosis
Features of Edwards?
Clenched hand w/ index finger overriding middle finger, and 5th finger overriding 4th finger, Meckel's diverticulum, malrotation, prominent occiput, low-set ears, rocker bottom feet (see this in Patau too)
How could you tell SCID apart from other congenital immune stuff?
Will have infection susceptibility characteristics of both T cell and B cell deficiencies -> so you get recurrent infections by bac, fungi, virus, OPPORTUNISTIC PATHOGENS -> failure to thrive and chronic diarrhea w/in 1st year of life
Infections characteristics of B cell deficiencies: extracel encapsulated bac (H. influenzae, Strep pneumo, Moraxella)
Infections characteristics of T cell deficiencies: Pneumocystis, chronic mucocutaneous candidiasis, toxo, crypto
Older pt starts addressing intern w/ first name b/c intern looks like her grandson, so intern starts addressing her b first name. What should an attending do?
Address the pt w/ Mr./Mrs. followed by last name
DON'T even ask if it's ok to start addressing her by first name (pt should always be the one to initiate lowering level of formality, not doctor)
What accounts for antiseptic properties of alcohols? Does it kill bacterial spores?
Disrupting cell membrane + denatures proteins
Doesn't kill spores
What accounts for antiseptic properties of chlorhexidine? Does it kill bacterial spores?
Disrupting cell membrane + coagulation of cytoplasm
Doesn't kill spores
Neurotoxic so don't use w/ eyes, ears, neurological procedures
What accounts for antiseptic properties of H2O2? Does it kill bacterial spores?
What accounts for antiseptic properties of iodine? Does it kill bacterial spores?
Halogenation of proteins and nucleic acids
What accounts for antiseptic properties of aldehydes?
Alkylating and X-linking DNA and proteins
Endocarditis by what 2 groups of bac is assc. w/ dental extraction?
Viridans group strep (on ALREADY ABNORMAL heart valves)
Dx of skin hyperextensibility + joints hypermobility + poor wound healing + easy bruising?
What are TATA and CAAT boxes considered? Where are they in the gene?
PROMOTER REGION (initiates transcription by serving as binding sites for transcription factors and RNA pol II)
TATA: 25 nucleotides upstream
CAAT: 70-80 bases upstream
Where does nitrogen source in urea cycle come from?
NH3 and ASPARTATE
What's the fx of glutamine?
Transports ammonia from peripheral tissue to kidney -> in the nephron glutaminase cleaves it and generates glutamate + NH4+ (which is then excreted in urine)
Molecules involved in neutrophil rolling? Tight adhesion/crawling? Transmigration?
Rolling: Sialyl Lewis X (PSGL-1) to L-selectin (on neutrophils) or E-selectin/P-selectin (on endothelium)
Tight adhesion/crawling: CD18 beta 2 integrins (Mac-1 and LFA-1) to ICAM-1 (endothelium)
Pt's family shows up during emergency situation (pt had MI and in OR) and ask how the pt is doing. They don't have ID's. Do you tell them?
Yes, HIPAA doesn't require ID. You don't need explicit permission in the case where pt is present and doesn't object, and in the case that the pt can't be present but sharing would be in pt's best interest -> only share general details tho
What 2 vitamins do you need to give infants who are exclusively breastfeed?
Vit K: usually given at birth
Vit D: b/c infants are usually shielded from the sun and it's not in breast milk
Iron is present in breast milk so don't need that
What is cholera toxin most related to?
Enterotoxigenic E. coli heat labile toxin
What orgs should you suspect if poop has mucus + sloughed epithelial cells?
Many erythrocytes and some leukocytes or w/ neutrophilic predominance?
Erythrocytes w/out leukocytes?
Many leukocytes w/ eosinophil predominance?
Many leukocytes w/ monocytic predominance?
Mucus + sloughed epithelial cells: V. cholera, Enterotoxigenic E. coli, Giardia
Many erythrocytes and some leukocytes or w/ neutrophilic predominance: Shigella, Salmonella, C jejuni, EIEC (enteroinvasive E. coli), Entamoeba
Erythrocytes w/out leukocytes: E. coli O157:H7
Many leukocytes w/ eosinophil predominance (Charcot-Leyden crystals): parasites besides Entamoeba and Giardia
Many leukocytes w/ monocytic predominance: Salmonella typhi
What 3 extracellular things does integrin react w/?
Fibronectin (also binds to GAG, matrix collagen)
Laminin (binds IV collagen = BM)
What does heparan sulfate do?
Mediates endothelial cell attachment to BM
What does keratan sulfate do?
Maintains type I collagen fibril organization in cornea
Keloid vs. hypertrophic scar? Does primary intention healing reduce the risk of developing keloid?
Hypertrophic scar is limited to the area of the wound and may regress spontaneously, and the collagen fibers are arranged in parallel (as opposed to disorganized like keloid)
No, primary intention healing is just as likely as any other wound to lead to keloid
What is southern blotting used for? Northen blot? Western blot? Southwestern blot?
Southern: DNA -> Identify DNA mutation (use labeled DNA probe to bind to DNA samples)
Southwestern: TF (DNA-bound protein)
What does brown adipocytes do? What are the differences between them and white adipocytes?
Thermal regulation in neonates (the oxidative phosphorylation is uncoupled w/ the protein thermogenin in these cells so instead of generating ATP in mito, they generate heat instead)
Compared to white adipocytes, brown adipocytes have more fat droplets and more mitochondria
What's the best approach in dealing w/ pt w/ somatic sx disorder (sick despite ruling out all biological possibilities)?
Increase frequency of regularly scheduled visits w/ primary care provider -> focus on functional improvement rather than sx elimination
A test w/ 95% specificity. How do you calculate the probability of having at least 1 positive result if you were to perform this test on 8 pts?
Probability of all 8 pts having negative results: 0.95^8
Probability of having AT LEAST ONE positive results: 1 - (0.95^8)
Always use this method whenever asked for probability of AT LEAST ONE event happening (calculate the opposite event first and subtract it from 1)
What role do pili play in the infection by N. meningococci?
Help them adhere to nasopharynx, oropharynx
Help them cross BBB
In what situation do you get non-immune mediated mast cell degranulation?
Opiates, vancomycin -> pseudoallergic rxn b/c doesn't involve drug-specific IgE
What measurement value is resistant to outliers?
(mean, median, range, SD, variance are usually all affected by outliers)
How do you calculate incidence?
# of new cases/# of ppl at risk
the # of ppl at risk has to be after subtracting # of ppl already w/ the disease
Example: disease A has 7,000 new cases this year. population is 4 mil, which contains 20,000 ppl already w/ disease A. Incidence is 7,000/3,980,000
How do you calculate disease specific mortality?
# of death attributable to a particular disease per year divided by TOTAL POPULATION (incl ppl already living w/ disease)
How do you calculate the rate of increase of a disease?
New cases per year - # of deaths or cures per year, divided by TOTAL POPULATION (incl ppl already living w/ disease)
80 yo w/ "mild cognitive impairment" brought in by her son and you suspect elderly abuse. What do you do?
Ask son to leave and ask pts additional question (assume cognitively impaired adults can communicate useful info)
3 bacteria whose polysaccharide capsules are conjugated to protein carriers as vaccines?
N. meningitidis: conjugated to mutant nontoxic diphtheria toxoid
H. influenzae: conjugated to N. meningitidis outer membrane protein complex
Strep pneumo: children PCV13 one is conjugated to inactivated diphtheria toxin (adult PPSV23 contains just capsular material)
Conjugation is to stimulate T-mediated Ig class switching and memory B cell generation (wouldn't get that w/ pure polysaccharide)
What form does tetanus vaccine comes in?
Tetanus toxoid (inactivated toxin, not conjugated)
What form does pertussis vaccine comes in?
Purified component of the bacteria + detoxified pertussis toxoid
What form does HBV vaccine comes in?
Purified inactivated HBsAg particles -> "recombinant surface protein vaccine" -> drawbacks similar to killed vaccine
What form does BCG vaccine comes in?
Live-attenuated vaccine from Mycobacterium bovis
UTI w/ acute onset dysuria and hematuria that resolves spontaneously w/in 3 days. Org?
Sx described is called hemorrhagic cystitis -> adenovirus is the most common viral cause of this in children (serotypes 11 and 21 of subgroup B)
Differences bet. Norwalk and Rotavirus?
Norwalk (calicivirus): epidemics of viral gastroenteritis worldwide
Rotavirus: most common cause of fatal diarrhea in children, esp in winter
Characteristics of hyperacute rejection vs. acute rejection vs. chronic rejection?
Hyperacute rejection: blood flow stops immediately after anastomosis of vessels (mediated by PREFORMED Ab), might also see vascular fibrinoid necrosis and neutrophil infiltration
Acute rejection (1-4 wks post transplant): host T cells are sensitized against graft MHC Ag -> immunosuppressive drugs target this phase; in lungs pulm & bronchial vessels are main targets
Chronic rejection (months-years): vascular stuff if kidney (scant inflammatory cells, interstitial fibrosis, fibrous intimal thickening of vessels -> mediated by host T cells + B cells + Ab); inflammation of small bronchioles if lung (bronchiolitis obliterans)
How does non-pathogenic Corynebacterium acquire virulence?
Lysogenization by a temperate bacteriophage -> Tox gene transferred -> can now cause pseudomembranous pharyngitis
What's lanugo? What condition is this seen in?
Fine, pale, dawny hair
Seen in anorexia
Non-lactose fermenting G- rods infecting indwelling bladder catheter?
P. aeruginosa (opportunistic)
Dx of kind w/ short stature + hypotonia + obesity + intellectual disability?
Prader-Willi syndrome -> maternal imprinting (paternal gene deleted)
Dx of happy kid w/ seizures + ataxia + severe intellectual disability?
Angelman syndrome -> paternal imprinting (maternal gene deleted)
How does mucormycosis present and what is the assc. condition?
Affects paranasal sinus so present w/ facial/periorbital, pain, headache, purulent nasal discharge, black eschar (necrotic tissue) on palate or nasal turbinates
See org branching at 90 degree angle
Strongly assc. w/ diabetic ketoacidosis, immunosuppression
Nutritional deficiency that can result in dilated cardiomyopathy?
Thaimine deficiency (wet beri beri)
Where is intermediate jx and what does it mediate?
Below tight jx in epithelial cells
Mediates cell-cell adhesion
How do most enveloped nucleocapsid viruses obtain their lipid bilayer? And what group of virus is the exception?
Most viruses (incl HCV, mumps): acquire from host PLASMA membrane
Exception is herpesvirus (incl CMV & EBV): acquire from host NUCLEAR membrane
What kind of vaccine is Lyme disease vaccine?
Recombinant bacterial outer surface protein (so similar to H. influenzae vaccine)
What kind of vaccine is typhoid vaccine?
Live attenuated bacteria
What food is assc. w/ food poisoning from preformed heat stable enterotoxin Staph aureus?
Custard, mayonnaise, processed/salted meats
What process is assc. w/ heterochromatin? Euchromatin?
Heterochromatin: DNA methylation -> low transcriptional activity
Euchromatin: histone acetylation -> high transcriptional activity
What's the process used to deactivate one X chromosome in female?
Lyonization: one X chromosome is heavily methylated and forms condensed heterochromatin at the nuclear periphery -> "Barr body"
Difference bet. carrier-mediated transport vs. channel proteins?
Carrier-mediated transport undergoes conformational changes as the substrate is transported
What structure fails to develop in DiGeorge? And what's the chromosome deletion?
Chr 22 deletion
3rd & 4th pharyngeal/branchial POUCHES fail to develop -> no thymsus, hypocalcemic, aortic arch abnormality, mandibular deformity)
What does septum transversum become?
Central tendon of diaphragm
Liver grows into this structure as an outpouching of foregut
What does Mycobacteria microscopic growth in parallel chains correlate most strongly w/?
That pattern of growth is called "serpentine cords" and is due to cord factor. It's a mycoside (2 mycolic acid molecs bound to disaccharide trehalose) and it works by inactivating neutrophils, damaging mitochondria, and inducing release of TNF.
What do sulfatides do for mycobacteria?
Inhibit fusion of lysosomes to phagosomes -> allow them to survive inracellularly
AUG sequence positioned near the beginning of mRNA and surrounded by Kozak sequence serves what fx? Mutation 3 bases upstream from AUG in this sequence is assc. w/ what condition?
Initiator for translation (mRNA binding to ribosome)
Protein targeting post-translation is achieved by AA sequence at what end?
N-terminal -> sequence removed once it reaches final destination
What type of hypersensitivity rxn does neutrophil play a role in?
Getting blanching of vein where NE is being infused + induration & pallor of tissue surrounding IV site. What is this and how do you fix it?
NE extravasation caused by a1-mediated vasoconstriction
Fixed by giving phentolamine (anti-a receptors)
How do you tell whether trisomy 21 is from nondisjunction of meiosis 1 or 2?
When doing restriction fragment length polymorphism on chr 21, you'll see 3 bands if nondisjunction is from meiosis I, and 2 bands w/ one being thicker if it's from meisis II (b/c inheriting sister chromatids which are the same size)
What's the p-value for statistically significant 95% CI? 99% CI?
95% -> p value p value
5 species that can cause enteric bacteremia?
E. coli, Salmonella typhi, Pseudomona, Klebsiella, Proteus
Blood & leukocytes in stool + non-lactose-fermenting, G- rods that doesn't produce gas or H2S? What's the mechanism causing disease? Transmission?
Mucosal invasion (Shigella is never part of normal gut flora) -> it also produces toxin, but this is NOT the main mechanism causing disease
What 2 bac causing GI sx can proliferate in LN?
Yersinia enterocolitica -> pseudoappendicitis
Salmonella typhi (in macrophages in Peyer's patches)
Type of collagen in granulation tissue vs. mature scar?
Granulation tissue: type III
Mature scar: type I
Where do you find type I collagen besides bone?
Tendon/ligament, dermis, cornea, blood vessels, dentin
Where do you find type II collagen besides cartilage?
Nucleus pulposus, vitreous humor
Where do you find type III collagen besides granulation tissue?
Reticular fibers in spleen, LN, bone marrow
Skin, lungs, intestine, blood vessels
What 2 potential risk factors of acquiring rickettsia rickettsia?
Tick-born so risk goes up w/
1. Contact w/ dogs
2. Exposure to wooded/grassy area
What's the risk factor of acquiring Mycobacterium scrofulaceum? What's the sx?
Environmental water source -> so get from swimming in a pond (usually children)
Lymphadinitis (usually cervical)
What drug is used for maternal prophylaxis if mom has AIDs?
Zidovudine (AZT, ZDV) -> nucleoside analog that inhibits reverse transcriptase (NRTI)
What's linkage disequilibrium and how do you know it's present?
A pair of alleles from 2 loci are inherited together in the same gamete more or less often than would be expected (not necessarily imply close physical proximity)
Know this by calculating probability of 2 alleles appearing together => product of frequency of one allele and another (NOT 2pq like Hardy-Weignberg b/c we're comparing 2 diff loci, so just pq)
If the probability shown is more or less than calculated value -> linkage disequilibrium exists
Multiple phenotypic presentation (ie diff organs) from single gene
2 organisms causing nongonococcal urethritis (NGU) and their differences from N. gonorrhea
Chlamydia: has cell wall but doesn't contain peptidoglycan, can't produce ATP on its own
Ureplasma urealyticum: NO cell wall at all, can produce ATP
This is why ceftrixone isn't effective against these (it targets peptidoglycan cell wall synthesis)
How are G+ and G- different in their way of acquiring resistance to beta-lactams?
G+ doesn't have outer cell membrane -> beta lactams can just reach cell wall w/out having to go inside cell -> so only resistance mechanism is to alter PBP
G- has outer cell membrane -> so one of the resistance mechanisms involves modification in porin proteins to prevent antibiotic entrance
How are lysine and leucine a unique AA?
Essential AAs that are strictly ketogenic -> not transaminated as an initial step of metab
Sx of zinc deficiency?
Acrodermatitis enteropathica (AR, periorificial and acral dermatitis + alopecia + diarrhea), growth retardation, infertility + might get nigh blindness too
How does body get rid of copper?
Hepatic excretion into bile
What are 5 diff E. coli virulence factors and diseases they create?
K1 CAPSULAR Ag: prevents recognition of bacterial Ag, complement fixation, and phagocytosis -> neonatal meningitis -> Ab generated against this is protective
P fimbriae: allows adhesion to urothelium -> UTI
Lipid A (in LPS): macrophage activation -> sepsis
Verotoxin: inactivates 60S ribosome (Shigella-like) -> enterohemorrhagic E. coli (bloody diarrhea)
Enterotoxin: watery diarrhea
2 cells w/ the most important role in containing TB infection
Th1 (CD4+) cells and macrophages -> why some ppl get caseous granuloma w/out sx after being exposed
What is power of a study? What variable is it related to?
Power: Ability to detect a difference bet. groups when a difference TRULY exists
Power = 1 - Beta
Beta is type II error (probability of concluding there's no difference bet. a group when the difference exists) = usually around 20%
What's a type I error and what is the equivalence reported?
Type I error = probability of concluding there's a difference when a difference does NOT exist
Correlates to p value
What does osmium tetroxide stain for?
Stains for fat (turns up black)
What does ricin inhibit?
rRNA of eukaryotic 60S subunit -> stops protein synthesis
3 variants of Turner syndrome and what went wrong in each
1. 45,XO (complete monosomy) from loss of parental X during mitosis, MEIOTIC nondisjunction
2. 45,XO/46,XX OR 45,XO/46,XY (mosaicism) from MITOTIC nondisjunction
3. 46,XX partial deletion of one or more arms of X (partial monosomy)
4. structural abnormalities of X chr like X fragments or isochromosome
What's responsible for protein primary, secondary, and tertiary structure?
Primary: peptide bonds
Secondary: hydrogen bonds (a-helix and b-pleated sheets)
Tertiary: hydrogen bonds, hydrophobic interactions, disulfide bonds (enhance ability to withstand denaturation), ionic bonds
Formula to calculate loading dose
Loading dose = Vd x Css / F
F = 1 in IV
Loading dose remains unchanged in pts w/ hepatic/renal impairment, it's the maintenance dose that you need to adjust
What do LTC4, LTD4, LTE4 do?
Vasocontriction, increases vascular permeability, bronchospasm
4 situations where disclosure of pt info doesn't need consent
reportable communicable disease
harming self or others
What does Vi Ag in salmonella do?
Prevents opsonization and phagocytosis
What direction does DNA polymerase form new daughter strand?
synthesizes from 5' -> 3' (so read the parent strand from 3' -> 5')
What proteins facilitate initial separation of dsDNA at the origin of replication for helicase?
DnaA protein and strand binding proteins (SSB)
What is dentinogenesis imperfecta and what condition do you see this in?
Small malformed teeth
See this in osteogenesis imperfecta
Transduction vs. transformation vs. conjugation vs. transposons
Transformation: takes up exogenous DNA (also use this term when viral DNA gets incorporated into host chromosome)
Conjugation: donor produces sex pilus
Transposons: mobile genetic elements that move gene between and w/in bac chromosome, plasmids, phages
What's the disease caused by Mycobacterium kansasii? What's the source of contamination?
Disease similar to MTB, acid-fast rods
Gets it from municipal drinking water system (not frequently found in nature)
Inheritance of andregenetic alopecia if X-linked recessive is not a choice?
Polygenic inheritance w/ variable penetrance
What happens to tRNA that's mischarged w/ incorrect AA?
Wrong AA will be incorporated into polypeptide
Some AA-tRNA synthetases have proofreading activity, but if it's past that phase and AA is charged, there's no AA proofreading during protein translation itself
What does nitroblue tetrazolium test for?
CGD -> neutrophils will fail to turn blue if NADPH oxidase deficiency
What does Staph coagulase do exactly?
Activates prothrombin -> conversion of fibrinogen to fibrin -> fibrin coats org -> resistance to phagocytosis
What different mechanism do viruses w/ SS, negative-sense RNA use for transcription?
Cap snatching: some viruses have endonuclease that cleaves 5'RNA fragments that are used to prime viral RNA for transcription by viral RNA polymerase
What does Tzanck smear detect? What about Papanicolaou smear?
Tzanck smear: HSV or VZV
Pap smear: HPV
What does hemadsorption test detect?
Influenza and parainfluenza viruses
3 mycobacterial virulence factors?
All need mycolic acids for synthesis
What can you use for poisoning by mercury, arsenic, gold?
Dimercaprol - DOC for arsenic poisoning
What can you use for poisoning by lead and mercury?
EDTA - DOC for lead and mercury poisoning
Sx of arsenic poisoning?
Garlic breath odor, stomach pains, vomiting, delirium
From inhibiting lipoic acid which is a cofactor for pyruvate DH and a-ketoglutarate DH
How do you calculate case-fatality rate?
Divides # of fatal cases by total # of PPL W/ DISEASE
(don't consider the total mortality or other #'s assc. w/ other diseases at all)
What does NF-KB do?
It's TF for cytokine production
What nucleotides are in tRNA? What does their 3' end and 5' have?
Acceptor stems have both 3' and 5' ends: 3' CCA tail (AA is bound to 3' terminal OH group), 5' terminal phosphate (terminal guanosine)
D arm: dihydrouracil
T arm (binding to ribosomes): thymidine (only RNA species containing this), pseudouridine, cytidine
Anticodon arm: complementary sequence to mRNA. It's read in 3'->5'
3 things involved in eukaryotic posttranscriptional modification? Where does this happen?
Poly A tail at 3' end (after AAUAAA sequence)
Methylguanosine cap at 5' end
Removal of introns
All happen in nucleus
4 things pts are given passive preformed Abs against after exposure?
"To Be Healed Rapidly"
Tetanus toxin, Botulinum toxin, HBV, Rabies
For HBV and rabies, combined passive and active immunizations can be given
What cells are CD14 positive and what is this receptor directly stimulated by?
Endotoxins/LPS can directly stimulate this w/out involving Th cells
What cells are CD56 positive?
Also CD16 positive -> binds Fc of IgG to kill via Ab-dependent cell-mediated cytotoxicity
What's a receptor for EBV on B cells?
What enzymes does arsenic inhibit?
Arsenic inhibits lipoic acid -> so enzyme pyruvate DH (linking glycolysis and TCA) and alpha ketoglutarate DH (TCA) are affected
What does one TCA cycle produce? How many ATPs?
One cycle produces 3 NADH + 1 FADH2 + 2CO2 + 1 GTP -> so (3 x 3) + (1 x 2) + 1 = 12 ATPs --> but used 2 ATP so really just generates 10 ATPs
Go thru cycle twice per glucose
Substrates/products in TCA?
"Citrate Is Krebs' Starting Substrate For Making Oxaloacetate"
Citrate (6C), Isocitrate (6C), a-Ketoglutarate (5C), Succinyl-CoA (4C), Succinate (4C), Fumarate (4C), Malate (4C), Oxaloacetate (4C)
3 ETC uncoupling agents?
Decreases proton gradient -> no ATP synthesis just heat production
2,4-dinitrophenol (illicit weight loss drug), aspirin (why get fever after overdose), thermogenin (brown fat)
What tissues are gluconeogenesis irreversible enzymes present in?
Liver, renal, and intestinal tissue
What kind of FA can serve to produce glucose and how?
Odd-chain FAs -> 1 propionyl-CoA can enter TCA as succinyl-CoA to serve as glucose source
Even-chain FAs can't produce glucose b/c they only yield acetyl-CoA equivalents
2 acidic AAs?
Acidic AAs are all about ASS
ASSpartate and glutamate (gluteus = ass muscles) -> negatively charged at body pH
Substrates/products in urea cycle?
"Ordinarily Careless Crappers Are Also Frivolous About Urination"
Ornithine + Carbamoyl phosphate, Citrulline + Aspartate, Argininosuccinate, Fumarate + Arginine, Urea
What are the sx of carnitine deficiency?
Can't transport LCFAs into mito -> accumulation, less mito beta oxidation -> less acetyl CoA produce -> less ketone bodies produced
Weakness, hypotonia, hypoketotic hypoglycemia
What can't urine test for ketones detect?
Apolipoproteins on chylomicron?
E (for uptake by liver cells), A-I (for LCAT activation), C-II (for lipoprotein lipase), B-48
Secreted from enterocytes w/ only ApoB-48, later get ApoC-II and ApoE from HDL
Apolipoproteins on chylomicron remnant?
E (for uptake by liver cells), B-48 (lost A-I and C-II)
Apolipoproteins on VLDL?
E (for uptake by liver cells), C-II (for lipoprotein lipase), B-100
Apolipoproteins on IDL?
E (for uptake by liver cells), B-100 (lost C-II from VLDL)
Apolipoproteins on LDL?
B-100 (lost E from IDL)
B-100 is required for receptor-mediated uptake of LDL by extrahepatic tissues
Apolipoproteins on HDL?
E (for uptake by liver cells), A-I (for LCAT activation), C-II (for lipoprotein lipase)
Enhancers/repressors location in the gene? What are their fx?
Location: anywhere (upstream, downstream, or w/in gene)
Fx: increases/decreases rate of transcription initiation thru protein binding and interactions w/ TF bound to promoter sequence
What happens in host cells and viral replication during abortive viral infection?
Little/no change in host cell
No viral replication
Difference bet. primary and reactivated HSV-1 infection?
Primary: fever, vesiculoulcerative gingiovostomatitis, cervical lymphadenopathy
Reactivation (from trigem ganglia): more limited -> cold sores
How does enzyme affect energy of rxn? What does Gibbs free energy tell you?
Enzyme reduces energy of transition state (so reduces activation energy) -> doesn't do anything w/ Gibbs
Gibbs: negative means spontaneous -> favors product, Keq will be > 1
Positive is opposite
If 0 Gibbs = no net concentration change
Why do you get anemia w/ Mycoplasma infection?
It shares Ag w/ RBC -> body mounts response against both orgs and own RBCs (cold agglutinins)
Differences bet. 5'->3' exonuclease and 3'->5' exonuclease?
5'->3' exonuclease: only DNA polymerase I has it (assc. higher # 5 w/ lower DNA polymerase 1)
3'->5' exonuclease: proofreading activity, see in DNA polymerase I, DNA polymerase III, viral RNA polymerase (HCV lacks this in its RNA polymerase tho) -> DNA synthesis is 5'->3', so think of this as "looking back" (reverse) to make sure it's doing its job right
What tissues can't use ketones?
RBCs and tissues w/out mitochondria (conversion of ketones to acetyl-CoA happens in mitochondria)
Liver -> no thiophorase (succinyl-CoA-acetoacetate CoA transferase) so can't get acetyl-CoA
What bacteria have "long branched saturated fatty acids"?
Described FA is mycolic acid
Sx and timeline of scarlet fever? And what does it predispose to?
Incubation period of 1-5 days -> gray-white exudates in pharynx (THIS SX NOT IN KAWASAKI), strawberry tongue
Then 1-2 days later -> scarlet spots/blotches (boiled lobster) of rash -> then sandpaper-like rash & circumoral pallor -> then desquamation
Predispose to rheumatic fever and glomerulonephritis
Cells that are important to limiting localized Candida infection vs. disseminated Candida infection?
Localized infections (oral thrush, esophagitis, cutaneous candidiasis, vulvovaginitis) -> T cells important!
Disseminated infections -> neutrophils important! (role in limiting hematogenous spread)
AA composition of collagen molecule?
Most abundant AA: glycine -> needs at every third AA of alpha chain in order to fold into triple helix
Other minor components are proline (creates bend in polypeptide chains important to forming alpha helix) and lysine (important to cross-linking to other collagen molecs)
What is psammoma body composed of? What are 4 things you see psammoma bodies in?
Composed of core dense calcification w/ surrounding collagen-fiber bundles
See in PSaMM: papillary thyroid carcinoma, serous papillary ovarian adenocarcinoma, meningioma, malignant mesothelioma
How do you calculate positive and negative likelihood ratio and what do they tell you?
LR+ = sensitivity / (1-specificity) -> tells you likelihood of having the disease given positive result
LR- = (1-sensitivity) / specificity -> tells you likelihood of having the disease given negative result
Unlike PPV & NPV, not assc. w/ prevalence!
Infection by what orgs is assc. w/ undercooked shellfish?
What kind of substance reduces Vmax but doesn't change Km?
Decreases just efficacy -> so either a noncompetitive antagonist or an IRREVERSIBLE competitive antagonist
What is usually the primary focus of cryptococcus? What is the most common manifestation?
Primary focus is usually lung. However it's usually asymptomatic there.
The most common manifestation is meningitis b/c CSF lacks components of alternative pathway -> so impaired phagocytosis of cryptococcus
What are transamination rxns and what vitamin do most transamination rxns require?
a-ketoacid + AA forms AA + a-ketoacid
ie oxaloacetate (a-ketoacid) + glutamate (AA) -> aspartate (AA) + a-ketoglutarate (a-ketoacid)
What does carnitine do? What does it need for synthesis?
AA that transport FAs into mito for beta-oxidation
Synthesized from lysine + methionine + vit C
What's the mechanism of toxins produced by C. difficile?
Both A and B inactivate Rho-regulatory proteins -> impaired signal transduction and actin cytoskeletal structure maintenance -> disruption of intercellular tight jx
2 examples of drugs assc. w/ mitochondrial toxicity?
Cyanide and NRTIs
What kind of vaccine is the active rabies vaccine?
Killed vaccine (the entire virus particles killed by beta-propiolactone)
How do you calculate SE from SD? What does 95% mean for SE?
SE = SD / square root of n
So 95% CI would still be +/- 2 SE just like it does w/ SD
Policies on using interpreters in medical settings?
Non-emergent settings (depressed pts in ER count too): wait for TRAINED interpreters
Emergent settings: can use friends/family, writing, hospital staff, anything that can help quickly
What molecule do you use as a marker for mast cell activation/anaphylaxis?
4 stages of sx of iron poisoning?
Stage 1: nausea, diarrhea, abd pain, hemorrhage (hematemesis and melena!), hypovolemia, shock
Stage 2: appears better
Stage 3: metabolic acidosis, hepatic dysfx, hypoglycemia
Stage 4: scarring of recovering GI tract
What yeast appears red on mucicarmine stain?
What enzyme allows you to synthesize ribose from fructose-6-P when you don't have NADPH from oxidative side of HMP shunt?
Transketolase and transaldolase from the nonoxidative portion of HMP shunt
What's one purpose of oxidative half of HMP shunt? Nonoxidative half?
Oxidative half = to generate NADPH for use in glutathione reduction rxn and enzymes involved in FA, cholesterol and steroid synthesis
Nonoxidative half = to make ribose 5-P from intermediates of glycolysis
What's a rare disease assumption?
Odds ratio approximates relative risk when disease prevalence is low
A graph of drug glucuronide conc (y) vs. drug dose (x) shows a rise then plateau. What does each segment represent?
The first linear segment w/ positive slope = first order kinetics = increase in PROPORTION (percentage) of drug is metab w/ increase in drug dose
The reflection point = where first order is changed to zero order
The plateau segment (enzyme saturation) = zero order kinetics = constant AMOUNT of drug is metab regardless of drug dose
Steps and locations of collagen synthesis?
RER: special sequence at N-terminus facilitates ribosomal binding to RER and guides growing pre-pro-alpha chains into RER -> then N-terminus signal peptide is cleaved -> proline and lysine hydroxylation, vit C required -> glycosylation w/ galactose and glucose -> central region flanked by globular N- and C-terminal extensions (propeptides) -> disulfide bond formation (triple helix procollagen molecule formed)
Golgi: send procollagen triple helix out of cell
Extracellular: Propeptides at N and C-termini are cleaved by procollagen peptidase to form insoluble tropocollagen molecs -> self-assembly into collagen fibrils that are then X-linked by lysyl oxidase
Where do you find Moraxella catarrhalis? What does it cause?
Normal flora of URT
Causes otitis media and sinusitis in healthy ppl
Might cause exacerbation of COPD
How do you prevent neonatal GBS sepsis?
Give INTRAPARTUM penicillin prophylaxis to mother
What type of hypersensitivity is acute serum sickness and what's the example of how you get this?
Type III HSR: so immune complex, neutrophils infiltration, fibrinoid necrosis, hypocomplementemia
Example: 7-14 days after starting infilximab for Crohn, present w/ fever, pruritic RASH & ATHRALGIAS
What does coefficient of variation quantify? How do you calculate it?
Quantifies reliability of a test
Calculated by SD divided by mean
Do you get more or less expression w/ histone DEacetylation?
Deacetylation -> less expression b/c chromatin is closed
Rules for dating FORMER pts?
Can do it if you're not a psychiatrist
When do you give H. influenzae b vaccine? What kind of immunity does it stimulate?
Beginning at 2 mo
Immunity during the first couple of months prior is acquired by transient maternal transplacental IgG
Vaccine stimulates HUMORAL immunity
What end does telomerase add to?
Should make sense since DNA synthesis occurs from 5' -> 3'
What do you use to stain diphtheria's metachromatic granules?
Aniline dyes (like methylene blue)
What neurotransmitters are inhibited by tetanus toxin?
GABA and glycine (both inhibitory)
A single mutation can cause orotic aciduria affects what 2 enzymes?
Orotate phosphoribosyl transerase and OMP decarboxylase -> they're separate active domain on a single polypeptide so a single mutation will cause dysfx of both
This type of orotic aciduria comes w/ megaloblastic anemia (unlike ornithine transcarbamylase deficiency) and need uridine supplementation.
2 orgs commonly isolated from intraabdominal infections?
B fragilis and E coli
Org isolated from infection from perforation of proximal bowel like peptic ulcer?
What's the org that cause diarrhea that can be passed on from domestic animals?
Can also be passed on from contaminated food (like undercooked poultry and unpasteurized milk)
What pts are prone to developing hypercalcemia and hypercalciuria?
pts w/ granulomatous disorders: sarcoidosis, TB, Hodgkin's, non-Hodgkin's
What AA makes NO?
What AAs make urea?
Arginine + aspartate
What AA makes heme?
Glycine and succinyl CoA
What AAs make creatine?
Glycine + arginine + SAM
What AAs make pyrimidine?
Glutamate + aspartate
What AAs make purines?
Glutamate + aspartate + glycine
What AA makes melatonin? Melanin?
Tryptophan -> serotonin -> melatonin (tryptophan also makes niacin)
Tyrosine -> thyroxine -> melanin (tyrosine also makes dopamine)
What does PAF do besides the obvious stuff?
Causes vasoconstriction, bronchoconstriction, enhannces leukocytes adhesion, chemotaxis, phagocytosis, degranulation
What molecs increase ESR?
IL-1, IL-6, TNF-a stimulate hepatic secretion of acute-phase proteins like fibrinogen -> fibrinogen makes RBCs form stacks and increases ESR
What 4 drugs can cause increased toxicity in slow acetylators?
Isoniazid, dapsone, hydralazine, procainamide
What does Klebsiella look like on gram stain?
Obv gram negative
Thick capsule seen as clear zone + mucoid growth
What does Klebsiella pneumonia classically affect?
Alcoholics: colonizes oropharynx followed by microaspiration, upper lobes commonly affected
What's a Samter's triad?
Asthma + aspirin hypersensitivity + nasal polyposis
From high-dose aspirin
Vertigo + tinnitus + hearing loss
Aspirin stimulates resp drive -> resp alkalosis -> salicylate accumulation -> metabolic acidosis
Enzymes in peroxisomes? What metabolic fx do peroxisomes do?
Oxidative enzymes like catalase, D-amino acid oxidase, and uric acid oxidase
Metabolic fx are beta oxidation of VLCFA and alpha oxidation of branched chain FAs like phytanic acid -> get Zellweger syndrome (can't properly form myelin in CNS) or Refsum disease (alpha defect -> phytanic acid accumulates -> avoid chlorophyll in diet)
Energy from beta oxidation is used to generate H2O2
Antibiotics that work on 50S ribosomes? 30S ribosomes?
50S: chloramphenicol, clindamycin, linezolid, macrolides
30S: tetracycline, doxycycline, aminoglycosides
What do tat gene and nef gene do for HIV?
tat gene: viral replication
nef gene: decreases MHC I expression on surface of infected cells
What gives collagen diversity in different tissues?
Variation in AA sequences in alpha chains
What do you need to supplement in media to grow mycoplasma?
What AAs are both glucogenic and ketogenic?
Phenylalanine, isoleucine, tryptophan
When do you typically seen nafcillin being used?
Skin and soft tissue infections (folliculitis, abscesses) typically caused by S. aureus (don't assc. folliculitis only w/ pseudomonas b/c S. aureus can cause this too!)
NOT food poisoning caused by the same org -> supportive tx only for that b/c it's a toxin-mediated illness and antibiotics won't do anything
Tenosynovitis + pharyngitis. What org should you be thinking about?
How can vit C deficiency present in children?
More severe -> might see subperiosteal and joint hematomas
What 2 rxns is thiamine important for?
Pyruvate -> acetyl CoA
Alpha-ketoglutarate -> succinyl CoA
2 components of telomerase?
TERT: reverse transcriptase
TERC: RNA template
How does Babesia divergens present? What region is high risk?
Malaria-like illness w/ predilection for asplenic pts
Endemic on NE coast of US
How does Isospora belli present?
Chronic, watery, profuse diarrhea in immunocompromised (AIDs especially)
What does fluid look like on CT?
Isodense w/ muscle -> so look for asymmetry bet. 2 sides b/c hematomas might blend in
3 biases named after ppl?
Hawthorne effect: subject changes behavior b/c they're aware they're being studied
Berkson's bias: selection bias (choosing inpatient as control group)
Pygmalion effect: researcher's belief in efficacy can potentially affect outcome (self-fulfilling prophecy)
What are HIV's pol gene mutations responsible for? Env gene mutations?
Pol gene mutations: acquired resistance to NNRTIs & NRTIs & protease inhibitors
Env gene mutationTs: escape from host neutralizing Ab
Example of drug that's excreted unchanged?
Drugs that undergo liver sulfate conjugation? What does that do?
Liver sulfate conjugation: phase II metab that transforms drug into more polar drug for excretion
Drugs: phenol and chloramphenicol
Drugs that undergo liver hydroxylation? What does that do?
Hydroxyl group is added to produce less lipid-soluble compounds
Drugs: pentobarbital and phenobarbital
Drugs that undergo liver hydrolysis? Plasma hydrolysis?
Liver hydrolysis (phase I metab): procaine, lidocaine, aspirin
Plasma hydrolysis: succinylcholine, tetracaine, remifentanil
Drugs that under go liver acetylation? What condition are they linked to?
Hydralazine and procainamide
Linked to drug-induced lupus
What vitamin deficiency is assc. w/ differentiation of specialized epithelia? And what are the results?
Deficiency = SQUAMOUS METAPLASIA from mucus-secreting columnar to keratinizing epithelium (see in ocular conjuctiva, respiratory, urinary, pancreatic, other exocrine ducts)
3 enzymes that start w/ the word "pyruvate" and the differences bet. them?
Pyruvate kinase: makes pyruvate from PEP
Pyruvate DH: oxidative phosphorylation (going forward from glycolysis to TCA cycle)
Pyruvate carboxylase: gluconeogenesis (converted to oxaloacetate for the purpose of going back up)
Defects involving 2 enzymes that cause homocystinuria and the similarities/differences bet. them?
Both will cause homocystinuria & thrombosis/atherosclerosis risk + Marfanoid habitus + lens subluxation (but downward & inward instead of upward and temporally like Marfan)
- More common: anything involving defects in cystathionine synthase (like enzyme deficiency or reduced affinity to its cofactor B6) -> supplement B6, B12, folate, cysteine, and restrict methionine
- Less common: homocysteine methyltransferase (methionine synthase) deficiency -> supplement methionine!
4 virulence factors of strep pneumo?
1. polysac capsule (quellung rxn -> halo around blue-stained bacterial cell when anti-capsular Ab and methylene blue dye are added to it) -> prevents phago
2. IgA protease
4. Pneumolysin -> causes pores in cell membrane -> cell lysis
What does M protein in strep pyogenes do?
Anti-phago, also binds fibrinogen (inflammatory mediator release and vascular leakage)
This is what serogroups are based on! -> M protein stimulates type-specific immunity
What 2 drugs cause acquired nyctalopia (night blindness)
Phenothiazines or chloroquine
What vitamin deficiency are you at risk of if you're on strict vegetarian diet?
What infection is assc. w/ transfusion?
CMV (lives in leukocyte-laden blood products)
What are secreted toxin and toxin bound to outer peptidoglycan of S. aureus?
Secreted toxin: hemolysin (destroy RBCs, neutrophils, macrophages, platelets)
Toxin bound to peptidoglycan: protein A (binds IgG and prevents complement activation)
What does Giardia look like? What's the major immune mechanism against it? And what do you see under the microscope?
Trophozoite is pear-shaped w/ multiple flagella and 2 nuclei; cysts are oval w/ up to 4 nuclei
Immune mechanism: CD4+ and secretory IgA (so anyone w/ IgA deficiency, agammaglobulinemia, and CVID are susceptible to chronic infection)
Histo: villus atrophy and crypt hyperplasia
How do you distinguish MAC from extrapulm TB? How do you treat it?
MAC: grows at higher temp (41 C) and widespread reticuloendothelial involvement -> so see marked anemia, hepatosplenomeg, elevated alk phos, elevated lactate DH
Tx: clarithromycin/azithromycin + rifabutin/ethambutol
Give prophylactic azithromycin if CD4+
2 characters that tell you for sure that tumors are anaplastic
Giant, multinucleated tumor cells
(bronchial epithelial cells producing keratin pearls isn't considered anaplastic, because it only requires metaplasia to be able to do that)
What is referral bias?
Populations differ due to admission or referral practices -> a study involving cancer risk factors at hospital specializing in cancer research might enroll cases referred from all over the country, while hospitalized control subjects w/out cancer may only come from local area
What is detection bias?
Risk factor itself may lead to extensive dx investigation & increases the probability that a disease is identified (ie smokers undergo increased imaging surveillance b/c of their smoking status)
What is allocation bias?
Bias from the way tx and control groups are assembled -> assigned in a non-random fashion
Example: study comparing oral NSAIDs and intraarticular corticosteroid injections might have obese pts preferentially assigned to corticosteroid group
Why do you get multiple organ involvement w/ MEN2 syndromes?
B/c they're all from neural crest cells!
So this should help you remember that parathyroid cells, parafollicular cells of thyroid (medullary), and adrenal medulla are from neural crest cells
Why don't you get more sx w/ fructokinase deficiency?
B/c hexokinase can still convert fructose to fructose 6-P -> this can go on to produce glycogen, glucose, or participate in pentose phosphate pathway
What 3 groups of bac produce hyaluronidase and what is it used for?
Produced by staph, group A strep, C. difficile
Used to digest extracel ground substance -> enhance ability to spread
Immunohistochemical stains for muscles?
How do you dx infection w/ C. tetani?
H&P, incl vaccine hx (booster recommended every 10 years)
Won't be able to do blood culture b/c only found locally at the wound
No serum toxin assay available
What Ig is found circulating as dimers? And where do you find it?
SECRETORY IgA (in serum will be a monomer) - the secretory piece of the molec is actually synthesized by epithelial cells while other parts are from plasma cells -> this part is to prevent degradation in secretions
Found in mucus, tears, saliva, colostrum
What's the strain of E. coli that doesn't ferment sorbitol or produce glucuronidase like other strains?
O157:H7 E. coli
6 bac toxins that activates adenylate cyclase?
B. pertussis (pertussis toxin)
B. anthracis (edema factor)
ETEC (heat labile toxin)
C. jejuni (enterotoxin)
B. cereus (heat labile enterotoxin)
V. cholerae (choleragen toxin)
2 bac toxins that activate guanylate cyclase?
ETEC (heat stable toxin)
Y. enterocolitica (enterotoxin)
3 ways to transport mitochondrial oxaloacetate (OAA) to cytosol
1. use mitochondrial PEPCK to convert it to PEP
2. transaminate it to aspartate
3. reduce it to malate
What do you do if pts ask you to perform a prodecure that's against your personal belief (like abortion)?
You don't have to do it, but have to provide referral who will perform the requested procedure
3 drugs that inhibit dihydrofolate reductase (prevents reduction of folic acid to THF)?
Trimethoprim: in bacteria
Methotrexate: in human
Pyrimethamine: in parasites
Most common source of E coli bacteremia?
Gut is the site of origin, but not typically the site of infection
2 disorders where you see urine turns dark upon exposure to air and how to distinguish them?
acute intermittent porphyria and alkaptonuria
AIP will have acute sx of abd pain and neuropsychiatric things, whereas alkaptonuria is pretty mild and will just have pigment depositions to diff parts in the body (ochronosis)
Does beta blockers have effect on circulating levels of catecholamines?
clonidine does because it stimulates a2 -> decreases catecholamines
Pancoast tumor causing face and right arm swelling & engorgement of subQ veins but only on one side. What vein does it compress?
Sx identical to SVC syndrome but on just one side of the body
Remember that external jugular joins subclavian -> then subclavian and internal jugular join to become brachiocephalic (which on the right side also drains right lymphatic duct)
What 5 orgs are ppl w/ CGD susceptible for?
Think CATALASE-positive (not oxidase, stop confusing them) -> so the usual ones in sketchy micro like staph aureus, nocardia, aspergillus
But also Burkholderia cepacia, Serratia marcescens
Ceft lip vs. cleft palate?
Cleft lip: maxillary prominences fail to fuse w/ intermaxillary segment (medial nasal prominence)
Cleft palate: palatine shelves of maxillary prominence fail to fuse w/ one another or w/ primary palate (which is formed from intermaxillary segment)
What 4 rxn should you be thinking about that need biotin (B7)? How do you get deficiency?
Biotin acts as CO2 carrier so used in enzyme that adds C to substrate -> the "carboxylases"
Beta-methylcrotonyl CoA carboxylase
Deficiency from excessive raw egg white consumption (avidin binds B7)
What factor most increases the risk of dying by suicide?
Access to firearms
Conditions assc. w/ impaired DNA repair?
Xeroderma pigmentosum (nucleotide base excision repair)
Fanconi anemia (AR hypersensitivity to X-linking agents)
Bloom syndrome (AR hypersensitivity to UV damage and chemo)
What do you use in Wilson's disease?
What process is responsible for double positive T cells?
TCR beta gene rearrangement (pro-T cells arrive at thymus as double-negative and undergo this process in thymic subcapsular zone)
Diff in Ag processing and structures of MHC I and MHC II?
MHC I: proteasome then Ag sent to RER by TAP (transporter associated w/ Ag processing) -> MHC I sent out to surface w/ Ag already bound; structure is heavy chain and B2 microglobulin
MHC II: sent out of RER w/ invariant chain -> invariant chain cleaved off after fusing w/ acidified phagolysosomes containing foreign Ag; structure is alpha and beta polypeptide chains
What's the co-stimulatory signal for T cell activation?
CD28 (on T cells)
B7 (on APC)
Example of how you get DNA base alterations? Enzyme sequence of BASE excision repair (NOT nucleotide excision repair)?
Nitrates consumption leads to deamination of cytosine (forming uracil), adenine (forming xanthine), and guanine (forming hypoxanthine)
Enzyme sequence: glycosylases (cleave altered base) -> endonuclease (cleaves 5' end of apurinic-apyrimidinic site) -> lyase (removes sugar phosphate group) -> DNA polymerase -> ligase
Where do you find teichoic acid?
Linked to peptidoglycan cell wall of G+ (none in G-)
What receptors mediate epinephrine actions on systolic BP and diastolic BP?
Systolic: increased by b1 & a1
Diastolic: decreased by b2 predominance at low dose, increased by a1 predominance at high dose
Pathologists who knew diabetes status of pts were 3 times more likely to interpret sample microscopy as diabetic nephropathy. What kind of bias is this?
What's a phenotypic mixing and how is it different from reassortment?
Both involve co-infection by 2 viruses in one host cells
Phenotypic mixing doesn't actually involve a change in genome -> you get mixing of viral surface proteins which might allow one virus to be infectious to the type of cell it couldn't infect before, but the next generation will actually be the original virus and can't infect those cells
Reassortment involves change in genome so the next generation will be infectious to a new type of cells as well
One virus inhibits the replication/release of a second virus that's infecting the same cell
How do you calculate attributable risk percent in the exposed? What is another name for it?
ARP = 100 x (RR-1) / RR
ARP = 100 x (risk in the exposed - risk in unexposed) / risk in exposed
Another name is relative risk reduction (RRR) if not doing percent and if talking about tx instead (the bottom # would be the control)
What does PAS stain for exactly?
Oxidizes C-C bonds forming aldehyades -> produce magenta color upon reacting w/ fuscin-sulfurous acid
So this is good at highlighting polysaccharides (fungal cell wall), mucosubstances, BM
Use distastase in conjunction if wanna wash glycogen away -> things like Wipple will be magenta w/ PAS and is disastase-resistance
What are 2 stains used for neutral lipids?
Sudan bblack (useful for frozen section)
How do you distinguish bet. NADPH oxidase deficiency and myeloperoxidase deficiency in CGD?
Use nitroblue tetrazolium and dihydrorhodamine flow cytometry testing -> in NADPH deficiency neutrophils won't turn blue (NBT) or fluorescent green (DHR), in myeloperoxidase both will be normal
Mechanism and cell death curve of exposure to radiation?
Kills cells by 2 mechanisms -> DNA double strand break and free radicals
Death curve: initially flat line followed by steep increase in cell death
The level of what molecule distinguishes bet. folic acid and B12 deficiency?
Methylmalonyl CoA -> only elevated in B12 (why get neuro sx)
Both will have elevated homocysteine
2-yo got treated for presumptive rotavirus-induced gastroenteritis. Now came back a few days after discharge w/ abdominal distention and diarrhea after each feeding. What enzyme defect should you be thinking about?
Secondary lactase deficiency (gastroenteritis damaged intestinal epithelium)
Tx of acute diphtheriae infection in order of importance?
1. antitoxin (passive immunity) -> most important on prognosis but ineffective against toxin that has already gained access to cardiac or neural cells
2. penicillin or erythromycin
3. DPT vaccine (active immunity)
What are intracellular orgs protected against?
Ab and complement! -> so think cell-mediated immunity anytime you have intracellular bac -> this cell mediated immunity might lead to macrophage activation and killing
What 2 intracel orgs block fusion of phagosomes w/ lysosomes?
TB and salmonella
What intracel org inhibits phagolysosome acidification?
What 2 intracel orgs escape from phagosome into cytosol?
Listeria and Shigella
What does listeriolysin O do?
Pore-forming toxin (secreted by Listeria) that is selectively activated w/in acidified phagosomes
Why do you use glucagon for beta blocker overdose?
It activates G protein on cardiac myocytes -> increased cAMP -> Ca2+ release from intracellular stores -> increased SA firing
In organophosphate poisoning, what can't you fix w/ atropine that you can w/ pralidoxime (if administered fast enough)?
Muscle paralysis -> b/c this is nicotinic effect and atropine only fixes muscarinic effects
Pralidoxime works on restoring AChE so works on both nicotinic and muscarinic effects
What's the cutoff for "fever" and what's the mechanism behind it?
> 38.3 C
Cytokines (IL-1, 6, TNF) enters brain and stimulates phospholipase A2 release of arachidonic acid -> PGE2 released and leads to increase in thermoregulatory set point in ant. hypothalamus (why NSAIDs and acetaminophen are antipyretics)
What's the cutoff for "hyperpyrexia" and how do you manage this?
> 40 C
Cooling measures first (cooling blanket) to prevent brain damage (purkinje cells of cerebellum esp sensitive to heat damage!)
Then antipyretics (NSAIDs; or oral and rectal acetaminophen equally effective)
Where does staph aureus colonizes in carriers?
Langhans cells vs. Langerhans cells?
Langhans cells: mutinucleated giant cell w/ horseshoe-shaped arrangement (nuclei derived from monocytic cell line that plays a role in granulomatous inflammation)
Langerhans cells: APC of skin
What 2 kinds of study do you calculate median survival for?
Cohort studies or clinical trials
What kind of study do you calculate prevalence odd ratio for?
What does secretory IgA do exactly?
Binds and inhibits action of pili & surface Ag that mediate mucosal adherence and penetration
Does NOT fix complement or opsonize
4 examples of orgs that don't need high infection dose to cause disease?
Shigella (b/c of its unique binding site on M cells -> usually unoccupied by normal gut flora so easier attachment and invasion)
The activity of what enzyme INCREASES in Lesch-Nyhan?
It's from decreased HGPRT activity (failure of purine salvage) -> so get PRPP accumulation (substrate) -> phosphoribosyl pyrophosphate amidotransferase uses this to form phosphoribosylamine in the first commited step of de novo purine synthesis (so activity of this enzyme is increased)
What's special about the final step in de novo purie synthesis?
IMP is converted to either AMP or GMP
GMP formation requires ATP and AMP formation requires GTP -> cross-regulation that decreases synthesis of one nucleotide when the other is deficient
2 ways to get toxo?
Oocysts: eat/drink water contaminated w/ cat feces
Pseudocysts: eat undercooked meat
What kind of antibiotics should you think about when usage makes bac more prone to disintegrate when placed in hypotonic solution?
Think about anything that works on peptidoglycan -> this is what makes bac resistant to osmotic stress
What orgs should you think about in acute orchitis in young adults? Older pts?
Young adults: C. trachomatis, N. gonorrhoeae
Older pts: E. coli
When do you give MMR?
What does ether/organic solvent test distinguish between?
Enveloped and nonenveloped viruses -> enveloped viruses will be inactivated by ether and organic solvents
What kinds of cells do medullary cords in LN contain?
B cells, plasma cells, macrophages
What kinds of cells do medullary sinuses in LN contain?
Reticular cells, macrophages
Where are subcapsular sinuses in LN?
Bet. capsule and cortex -> connects w/ afferent lymphatic vessels and cortical sinuses (which connect to single efferent lymphatic channel at hilum)
Granuloma formation 2 wks post laceration. Normal or what's wrong?
Not normal -> by now should get the start of maturation phase (fibrosis)
Granuloma formation prob due to foreign bodies (like retained suture) -> shows up clinically as tender erythematous brown/purple papule/nodule/plaque
What is orotic acid a precursor of?
What is a frequent site of nosebleed called? And what arteries form it?
Kiesselbach's plexus - ant. part of nasal septum
Formed from sphenopalatine artery (branch of third part of maxillary) + ophthalmic artery + facial artery
5 AAs that are nonpolar. Where would you see these?
Valine, alanine, isoleucine, methionine, phenylalanine
Prob see these on transmembrane region of receptors (bc they're hydrophobic)
What should you give animals deprived of folic acid to reduce erythroid precursor apoptosis?
This is b/c the rxn generating dTMP de novo needs folic acid; so giving thymidine will help shunt dTMP production from de novo pathway to salvage pathway (thymidine kinase)
What AA does biosynthesis of dUMP (pyrimidine precursor) need?
2 types of rxn that B6 is important for?
What do you need in PCR rxn? What are the steps?
DNA template, 2 primers (need to know the FLANKING sequence not the actual target sequence), heat-stable DNA polymerase, deoxynucleotide triphosphates
Steps: heating (DNA strand denaturation), cooling (primer annealing), rewarming (primer extension and DNA syntehsis)
What do you need in RT PCR rxn?
cDNA (produced by reverse transcriptase enzyme using mRNA as template)
Don't need to know sequence of cDNA tho
After normal control period, blood flow to the extremity of anesthetized animal is completely occluded for 1 minute. When the occlusion is released, blood flow increases abruptly and exceeds the control value for several minutes (reactive hyperemia). After an appropriate recovery period, the procedure is repeated and the extremity is actively exercised during the occlusion period. What would describe the reactive hyperemia after the second occlusion compared with that after the first occlusion?
Exercise will increase production of waste products (lactate, CO2, etc) -> more dilatation of local circulation -> more reactive hyperemia after clamp is removed